P1421: THE EFFECT OF HEMATOPOIETIC STEM CELL TRANSPLANTATION ON CEREBRAL PERFUSION AND OXYGEN METABOLISM IN PATIENTS WITH SICKLE CELL DISEASE
Authors: Liza Afzali-Hashemi, Elisabeth Dovern, Koen P. A. Baas, Anouk Schrantee, Aart J. Nederveen, Erfan Nur, Bart J. Biemond
Journal: HemaSphere (2023)

Topic: 26. Sickle cell disease Background: Sickle cell disease (SCD) is complicated by a high prevalence of silent cerebral infarcts (SCI) which increases with age. Hematopoietic stem cell transplantation (HSCT) is currently the only curative treatment for patients with SCD. Whereas several studies have shown that the markers of anemia and hemolysis normalize after HSCT, little is known about the effects of HSCT on cerebral hemodynamics and oxygen metabolism. Previous work studying these parameters in SCD patients reported increased cerebral blood flow (CBF) to compensate for anemia in order to maintain adequate oxygen delivery (OD). On the other hand, oxygen extraction and consumption have been found to be lower compared to controls. Aims: In this work, we aimed to investigate the effect of HSCT on CBF, OD, oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO2) using MRI in addition to the hematological parameters in adult patients with SCD. Methods: We included 17 adult patients with SCD (13 HbSS, 3 HbSβ0 and 1 HbSβ+; mean age: 25 years) who underwent an MRI scan before and after (median time before: 3 months and median time after: 10 months) non-myeloablative matched sibling donor or haplo donor HSCT. On the day of the MRI scans, parameters of anemia and hemolysis including hemoglobin, reticulocytes, LDH, and total bilirubin were determined. Whole brain (WB) CBF was measured using time-encoded pseudo-continuous arterial spin labeling (te-ASL). Venous blood T2 in the superior sagittal sinus was measured using T2-Relaxation-Under-Spin-Tagging (TRUST). OEF was calculated from arterial saturation measured by pulse oximetry and venous saturation calculated from the TRUST-derived blood T2. OD was calculated from CBF and oxygen content, where oxygen content was calculated from hemoglobin and arterial saturation. CMRO2 was calculated as: CMRO2 = OD × OEF. Results: Hemoglobin levels (9.3±1.1 vs 12.8±1.0 g/dL; t=-8.7, p<0.01) significantly increased and LDH (330±141 vs 216±141 U/L 37˚C; Z=-3.2, p<0.01), reticulocytes (182.7±124.7 vs 93.6±45.0 109/L; Z=-3.4, p<0.01), and total bilirubin (2.2±1.7 vs 0.3±0.2 mg/dL; Z=-3.6, p<0.01) significantly reduced to values found in healthy controls after HSCT. At follow-up, 12 patients were on sirolimus while 5 patients were scanned >1 year post-HSCT and not using sirolimus anymore. WB CBF significantly decreased after HSCT in SCD patients and was comparable to the CBF values of healthy controls (Fig. 1A). OD did not change after HSCT and was comparable to healthy controls (Fig. 1B). OEF increased after HSCT and reached comparable levels as healthy controls (Fig1C). CMRO2 significantly increased after HSCT in SCD patients but was still significantly lower compared to the controls (Fig. 1D). Patients that were scanned > 1-year post-HSCT without sirolimus, appeared to have a higher CMRO2 compared to patients with sirolimus (2.8±0.2 vs 2.4±0.4). However, this group was too small to perform statistical analyses. Conclusion: In this study, we have shown that CBF and OEF are normalized after HSCT in adult SCD patients. Although CMRO2 increased after HSCT, it did not reach the CMRO2 levels of the healthy controls, but in patients >1 year post-HSCT without sirolimus, CMRO2 further increased, close to CMRO2 levels in controls. Whether the higher CMRO2 values >1 year post-HSCT are related to sirolimus or slow reversibility of CMRO2 despite normalization of hemoglobin levels after HSCT, remains to be determined. Looking ahead, follow-up scans need to be performed to determine whether this normalization of cerebral oxygen metabolism will prevent future cerebral (silent) infarctions.Figure 1: Dot plots of WB CBF (A), oxygen delivery (B), OEF (C), and CMRO2 (D). Error bars denote the mean and standard deviation Keywords: Adult, Allogeneic hematopoietic stem cell transplant, Magnetic resonance imaging, Sickle cell disease